The present invention relates to analytical chemistry and, more particularly, to conductivity detectors used, for example, to detect sample fluid components as they flow in a channel through a detection region. A major objective of the invention is to provide for simpler and more economical contactless conductivity detection.
Much of modern progress in the medical, environmental, forensic, and other sciences can be attributed to advances in analytical chemistry. One important class of analytical tools separates components of a sample fluid (typically, a mixture of sample components and non-sample components such as carriers, buffers, and surfactants) by moving them at different rates along a separation channel. Once the components are separated, it is usually desirable to quantify, and, perhaps, identify the components. This typically requires detection of the components. Detectors are available to monitor certain parameters, such as conductivity, fluorescence, or absorption of ultra-violet (UV) electro-magnetic energy as the components pass through a detection region.
Conductivity detection is appealing for electrophoresis, in which components are separated by an electric field according to their electrophoretic mobilities. Components separated by electrophoresis necessarily have a measurable electrical conductivity associated with their electrophoretic mobilities. More generally, conductivity detection is useful for detecting the components with measurable conductivity regardless of how they arrive at the detector region.
Conductivity detection can be implemented by locating electrodes on the interior walls of an electrophoretic channel, in direct contact with the sample fluid. Typically, xe2x80x9ctransmitxe2x80x9d (or xe2x80x9cdrivexe2x80x9d) and xe2x80x9creceivexe2x80x9d (or xe2x80x9cdetectionxe2x80x9d) electrodes oppose each other across a transverse width or diameter of the electrophoretic channel. However; since the electrodes are in contact with the sample fluid, electrochemical reactions at the electrodes can affect both the electrodes and the sample. Such interaction can cause undesirable artifacts within a run and undermines repeatability between runs. This undesirable interaction between sample and electrodes is avoided by xe2x80x9ccontactlessxe2x80x9d conductivity detection.
Contactless conductivity detection is taught by Jose A. Fracassi da Silva and Claudimir L. do Lago xe2x80x9cAn Oscillometric Detector for Capillary Electrophoresisxe2x80x9d, Analytical Chemistry, vol. 70, 1998, pp. 4339-4343; Jirxc3xad Vacik, Jirxc3xad Zuska and Iva Muselasova, xe2x80x9cImprovement of the Performance of a High-Frequency Conductivity Detector for Isotachophoresisxe2x80x9d Journal of Chromatography, 17,322, 1985, 5 pages; Andress J. Zemann, Erhard Schnell, Dietmar Volger, and Gunther K. Bonn, xe2x80x9cContactless Conductivity Detection for Capillary Electrophoresisxe2x80x9d Analytical Chemistry, V. 70, 1998, pp. 563-567. In addition, an antisynchronously driven contactless conductivity detector is the subject of commonly owned U.S. patent application Ser. No. 09/576,690 filed May 23, 2000, entitled xe2x80x9cSample-analysis system with antisynchronously driven contactless conductivity detectionxe2x80x9d by Gary B. Gordon and Tom A. van de Goor.
In contactless conductivity detection, electrodes are capacitively coupled to the sample fluid through a channel wall. To this end, the electrodes can be formed on the exterior surface of the channel wall. Since the electrodes are not in contact with sample fluid, artifacts due to chemical interactions at the electrodes are eliminated and reproducibility is improved.
Since channel conductivity is measured through channel walls, detection sensitivity is an issue for contactless conductivity detectors. For many contactless conductivity detectors, sensitivity is maximal at a peak frequency, and falls off at lesser and greater frequencies. Unfortunately, the peak frequency typically varies with fluid conductivity, which is the parameter to be measured and thus is unknown. This can make the detector output difficult to interpret. Moreover, sensitivity can suffer when the detection frequency is not properly matched to the sample fluid.
The drive frequency can be swept to ensure each sample component is matched with its peak frequency. To ensure optimal detection sensitivity, the detection electronics can be tuned synchronously with the drive electronics. While this approach is workable, it adds considerably to the expense and complexity of a contactless conductivity detector. In addition, the range of the frequency sweep limits the range of conductivities that can be detected. What is needed is a simpler and more economical approach to contactless conductivity detection.
The present invention provides a contactless conductivity detector in which a xe2x80x9csignalxe2x80x9d electrode is used to both drive the excitation signal and sense the response. In other words, the same electrode is used for both transmission (drive) and reception (detection). One or more ground electrodes hold the sample fluid at a distance from the signal electrode at a known potential (AC ground). Drive electronics include a sense resistor and an oscillator coupled to the signal electrode through the sense resistor. Detection electronics read the signal generated at the signal electrode.
The signal electrode is the central node of a voltage divider, lying between the sense resistor and the resistance associated with the sample fluid extending between the signal electrode and the ground electrode. The AC amplitude at the voltage-divider node varies with the fluid""s electrical resistance, which is the reciprocal of its conductivity. By monitoring the AC amplitude at the signal electrode, the fluid conductance can be characterized over time; thus, separated components can be detected serially as they pass a region of a fluid channel monitored by the detector.
Where a capillary tube is used for the fluid channel, there can be ground electrodes both upstream and downstream of the signal electrode. Conveniently, the ground electrodes can be monolithic (i.e., part of) the metal housing that electrically isolates the detector electronics from external electrical influences. Alternatively, ground electrodes can be fabricated on the capillary walls. In the alternative case, the housing can contact the ground electrodes. In either case, the capacitance of the ground electrodes can be very large, essentially providing an AC ground potential in the fluid channel at the frequency of operation. In addition, a more compact detector is provided for, since only one electrode (the signal electrode) need be in the interior of the housing (as opposed to two or more in the prior art).
In the case of a planer embodiment, the signal electrode, the drive electronics, and the detection electronics can be conveniently fabricated and connected on one side of the channel. Only a ground electrode and a ground connection need to be defined on the opposing side. This topology greatly simplifies manufacture of the planar detector, with concomitant economic benefits.
Serendipitously, the inventive detector provides a rather flat response to conductivity over a range of frequencies. This means that a single drive frequency can be used throughout a sample run. The frequency sweep electronics required to optimize some prior art contactless conductivity detectors are not required. As a result, simpler and more economical conductivity detection is provided. These and other features and advantages of the invention are apparent from the description below with reference to the following drawings.